Social demographics determinants for resistome and microbiome variation of a multiethnic community in Southern Malaysia.

The prevalence of antibiotic-resistant bacteria in Southeast Asia is a significant concern, yet there is limited research on the gut resistome and its correlation with lifestyle and environmental factors in the region. This study aimed to profile the gut resistome of 200 individuals in Malaysia using shotgun metagenomic sequencing and investigate its association with questionnaire data comprising demographic and lifestyle variables. A total of 1038 antibiotic resistance genes from 26 classes were detected with a mean carriage rate of 1.74 ± 1.18 gene copies per cell per person. Correlation analysis identified 14 environmental factors, including hygiene habits, health parameters, and intestinal colonization, that were significantly associated with the resistome (adjusted multivariate PERMANOVA, p < 0.05). Notably, individuals with positive yeast cultures exhibited a reduced copy number of 15 antibiotic resistance genes. Network analysis highlighted Escherichia coli as a major resistome network hub, with a positive correlation to 36 antibiotic-resistance genes. Our findings suggest that E. coli may play a pivotal role in shaping the resistome dynamics in Segamat, Malaysia, and its abundance is strongly associated with the community's health and lifestyle habits. Furthermore, the presence of yeast appears to be associated with the suppression of antibiotic-resistance genes.

Experimental evolution of local parasite maladaptation.

Sign and magnitude of local adaptation in host-parasite systems may vary with ecological, epidemiological or genetic parameters. To investigate the role of host genetic background, we established long-term experimental populations of different genotypes of the protozoan Paramecium caudatum, infected with the bacterial parasite Holospora undulata. We observed the evolution of an overall pattern of parasite local maladaptation for infectivity, indicating a general coevolutionary disadvantage of this parasite. Maladaptation extended to host populations with the same genetic background, similar to extending from the local to a higher regional level in natural populations. Patterns for virulence were qualitatively similar, but with less statistical support. A nonsignificant correlation with levels of (mal)adaptation for infectivity suggests independent evolution of these traits. Our results indicate similar (co)evolutionary trajectories in populations with different genetic backgrounds. Nonetheless, the correlated clines of genetic distance and parasite performance illustrate how genetic background can shape spatial gradients of local adaptation.

Glucorticoid resistance in murine lymphoma and thymoma lines.

The thymoma line W7 contains 30,000 dexamethasone-binding sites per cell and gives rise to glucocorticoid-resistant variants at a frequency less than 1.6 X 10(-9); the lymphoma S49 contains one-half that amount of receptor, is resistant to low concentrations of dexamethasone, and gives rise to fully resistant variants at high frequency. These results suggest that S49 is functionally haploid (r+/-) for a gene coding for the receptor while W7 appears diploid for that locus (r+/+). Derivatives of the W7 (r+/+) line, selected for resistance to low concentrations of dexamethasone, have the same properties as S49. These putative W7's (r+/-) give rise to the same types of receptor variants as S49 and in the same proportion; 80 to 90% are "receptorless" (r-) while 10 to 20% are "nuclear transfer defective" (nt-). A total of 127 variants resistant to high concentrations of dexamethasone were derived from the W7 (r+/+) line after mutagenesis. All are receptor variants but N-methyl-N'-nitro-N-nitrosoguanidine and ethyl methanesulfonate induce only 60 to 70% r- variants, confirming the presence of two r+ alleles in the parental line. Ultraviolet light induces a higher proportion (87%) of r+ variants, as expected from the introduction of breaks and deletions in DNA.

Identification of a alpha-NeuAc-(2----3)-beta-D-galactopyranosyl N-acetyl-beta-D-galactosaminyltransferase in human kidney.

Microsomal preparations from human kidney were found to contain enzymic activity capable to transfer N-acetylgalactosamine from UDP-N-acetylgalactosamine to native bovine fetuin. The acceptor structures on the fetuin molecules were identified as N- as well as O-linked glycans with a markedly higher incorporation into the N-linked carbohydrate chains. Analysis of the alkali-labile transferase products by thin-layer chromatography indicated that the enzyme is able to synthesize structures having mobilities identical with those found on glycophorin from Cad erythrocytes. Mild acid treatment and enzymic hydrolysis with N-acetylhexosaminidase from jack beans of the N-linked transferase products suggested that beta-D-GalpNAc-(1----4)-[alpha-NeuAc-(2----3)]-beta-D-Galp-(1----s tructures were formed by the enzymic reaction on both N- and O-linked acceptors. The enzyme might, therefore, be involved in the biosynthesis of Sda (and Cad) antigenic structures. By use of various oligosaccharides, glycopeptides, and glycolipids having well characterized carbohydrate sequences, the acceptor-substrate specificity of the N-acetylgalactosaminyltransferase was determined. The enzyme generally recognized alpha-NeuAc-(2----3)-beta-D-Gal groups as acceptors, but in a certain conformation. Thus, tri- and tetra-saccharide alditols, native human glycophorin A, and GM3 were not acceptor substrates although they carry the potential disaccharide acceptor unit. When these structures were presented as sialyl-(2----3)-lactose or as a tryptic peptide from glycophorin A, they were shown to be rather good acceptor substrates for the N-acetyl-beta-D-galactosaminyltransferase from human kidney.

Free radicals generated by electrolysis reduces nitro blue tetrazolium in isolated rat heart.

Oxygen free radicals (OFR) are highly cytotoxic when produced in the myocardium under certain pathological conditions. In isolated rat hearts perfused retrogradely, OFR were generated by electrolysis of the Krebs-Henseleit buffer (two platinum electrodes, DC current, 10 mA, 1 min). In order to find evidence that OFR are produced, we used nitro blue tetrazolium (NBT) a soluble compound which yields a dark blue formazan pigment in the presence of reducing agents. Hearts were subdivided into: control, electrolysed, NBT (3.3 mg/ml) perfusion during electrolysis in the presence or absence of scavengers. The xanthine-xanthine oxidase (XXO) system known to produce superoxide radical was used as a reference. Specimens were fixed with formaldehyde and stained with eosine or Kernechtrot in preparation for light microscopical examination. Several areas of acute necrosis expressed by hyalinisation and loss of striation were observed in electrolysed hearts which present a pattern of wavy disrupted myofibers and an increase in interstitial spaces. A very faint deposition of formazan was observed in some rare areas of NBT perfused heart. Only the electrolysed group perfused with NBT and the one perfused with XXO plus NBT presented an extensive formazan deposition, mostly in the areas of fibre necrosis. Formazan was barely detectable when superoxide dismutase plus catalase were perfused in the XXO system, while it was still apparent when perfused in electrolysed hearts. These results support the hypothesis that electrolysis can be used to generate different species of OFR and to evaluate the protective action of scavenger and antioxidants against OFR-induced myocardial damage.

Is the exhaustion time at maximal aerobic speed an index of aerobic endurance?

The velocity of the last stage of the Montreal Track Test (MTT) has been measured in fifteen well trained runners. This velocity (vMTT) was assumed to be close to maximal aerobic running speed. In three different sessions, the subjects ran up to exhaustion at velocities corresponding to 95, 100 and 105% vMTT. The exhaustion time at 100 % vMTT (tlim100) was assumed to be an estimation of the exhaustion time corresponding to maximal aerobic speed. The relationship between exhaustion time (tlim) and distance (Dlim) in the case of running exercises at constant velocity until exhaustion can be described by a linear relationship (Dlim = D + b*tlim). The slope of the relation corresponds to a velocity (vcrit) which can be sustained for a long time. The values of vcrit were calculated from the results of running exercises performed at 95, 100 and 105% of vMTT. The present study showed that tlim at 100% vMTT (tlim100) was negatively correlated with vMTT and vcrit but that D and ratio vcrit/vMTT were independent of vMTT. A theoretical study based on models previously proposed for oxygen kinetics during supramaximal exercises (exponential model and Margaria's model) demonstrates that this negative relationship between vMTT and tlim100 can be explained by the kinetics of the accumulation of oxygen deficit (O2 def). tlim100 should also depend on VO2max, maximal oxygen deficit (Max O2 def) and the relative importance of anaerobic energy when a VO2 plateau is reached. Moreover, the value of tlim100 largely depends on the accuracy of the assessment of vMTT. Consequently, the exhaustion times corresponding to the different estimations of maximal aerobic speed on a track or a treadmill cannot be considered as valid indices of aerobic endurance.

[Psychotherapy with mothers and infants in problem families]. / Psychotherapie mit Müttern und Säuglingen in Problemfamilien.

This article reports on a project in which mothers living in conditions describable as suproletarian are given psychotherapeutic treatment alongside practical care. The special feature of this system of comprehensive care for mothers from so-called "hard-to-reach-families" is that it begins during pregnancy, is instituted via the agency of midwives and that the therapeutic sessions are designed on a long-term basis and take place in the mothers' own homes. In two detailed case reports the authors describe their methods and define the objectives pursued by this project - the stabilization of the mothers in their family life situation and the prevention, from birth, of disturbances and disabilities otherwise to be anticipated in the children themselves.

[Live oral typhoid vaccine Ty 21 a. An original method of manufacturing and distribution]. / Vaccin typhoïdique oral vivant Ty 21 a. Une méthode originale de fabrication et de distribution.

Oral immunization against typhoid using Ty 21 a strain did not meet the anticipated success. This vaccine is too expensive for countries which actually need immunization. The suitable form of the vaccine is not yet clearly defined. Our proposal therefore is to give up freeze-drying and to use fresh suspended live bacilli. We have established that this form is stable enough (at least one week at + 4 degrees C) to allow necessary controls and good dispatch. More, the colonization of digestive tract should be easier when the vaccine is given as a liquid than as capsules with a dry content.

[The Constantinople Imperial Bacteriology Institute]. / L'Institut Imperial de Bacteriologie de Constantinople.

The Constantinople Imperial Bacteriology Institute (CIBI) allowed the development of a common medical effort between France and Turkey at a time when the main European powers were competing to have an influence on the Ottoman Empire. In 1887, Turkey sent Zoreos Pacha, a medical doctor, to Paris to learn anti-rabies immunization techniques, and he started a rabies control institute after his coming back. In 1893, a cholera epidemic in Constantinople was vanquished by A. Chantemesse, sent by Pasteur, and France was allowed to start another microbiologic Institute. The first director of this Constantinople Imperial Bacteriology Institute was Maurice Nicolle. A brillant man, but suffering from a lack of diplomacy; he encountered numerous difficulties and regularly threatened to turn in his resignation. His successor, Paul Remlinger, arrived in 1900. His main research topic was rabies, and he became later a world-class expert on the subject. His position was taken over in 1911 by Paul-Louis Simond, unjustly forgotten nowadays despite his major discovery in 1898 showing that the plague was transmitted by ratfleas. The next director was a veterinary doctor, P. Forgeot, but his tenure was cut short by World War I, and he was the last French director of the CIBI. Since that time, Turkey has felt some gratitude towards France for its medical efforts. It organized in 1957 in Istambul a very congenial celebration for the 70th anniversary of the Rabies Control Institute, which numerous Pasteur Institute alumni attended. There is a clear contrast between the CIBI, the target of many intrigues and hostile maneuvers, and the North African Pasteur Institutes, which were making crucial discoveries during the same period. This contrast was mostly due to the absolute power of the Sultan, who would arbitrarily oppose some directors decisions, whereas the French government allowed the balanced growth of the Pasteur Institutes in territories under his control.

[In vitro titration of tetanus antitoxin]. / Titrage in vitro de l'antitoxine tétanique.

In vitro methods are used as an alternative to the expensive and time-consuming official method in mice for the titration of tetanus antibodies. Numerous techniques have been developed and used for this purpose, but with mixed results. The difficulty is to get good correlation with in vivo units whatever the vaccinal status of the individual. Today, some of these serological techniques have been virtually abandoned in favor of others which are becoming widespread. RIA is still used, but only in laboratories which already have the necessary equipment and skill. It is gradually replaced by ELISA, a rather delicate technique which however has kept its promises and is amenable to further progress. Passive haemagglutination has been greatly improved by the use of turkey erythrocytes. With this modification, this technique becomes reliable and sensitive and is apparently able to give good results for a large number of sera in case of mass investigation as well as for a quick estimate of the protective level in an individual.

[In vivo titration of tetanus antitoxins]. / Titrage in vivo des antitoxines tétaniques.

The theoretical background and the practical techniques of assay of tetanus antibodies on mice by the L+ toxine procedure, is precisely described in detail. Basing the arguments on certain aspects of the method, the accuracy of the test is estimated and its reproducibility is assessed, in terms of both in vivo and in vitro titrations.

Continuous microcarrier-based cell culture in a benchtop microfluidic bioreactor.

Microfluidic bioreactors are expected to impact cell therapy and biopharmaceutical production due to their ability to control cellular microenvironments. This work presents a novel approach for continuous cell culture in a microfluidic system. Microcarriers (i.e., microbeads) are used as growth support for anchorage-dependent mammalian cells. This approach eases the manipulation of cells within the system and enables harmless extraction of cells. Moreover, the microbioreactor uses a perfusion function based on the biocompatible integration of a porous membrane to continuously feed the cells. The perfusion rate is optimized through simulations to provide a stable biochemical environment. Thermal management is also addressed to ensure a homogeneous bioreactor temperature. Eventually, incubator-free cell cultures of Drosophila S2 and PC3 cells are achieved over the course of a week using this bioreactor. In future applications, a more efficient alternative to harvesting cells from microcarriers is also anticipated as suggested by our positive results from the microcarrier digestion experiments.